Investigating whether a living subject is affected by certain conditions such as cancer, other pathological processes or diseases is often done initially by a physician who may observe the subject, possibly by eye or using observational tools such as endoscopes. If this visual observation identifies areas of tissue that appear to merit further investigation the physician may take a biopsy of the tissue. The biopsy may then be prepared for microscopic examination by a pathologist. A disadvantage of this procedure is that taking a biopsy is an invasive procedure. Also, transporting, tracking, preparing and examining the biopsy sample can be expensive and time consuming. There is a need for more efficient ways to perform diagnosis and/or screening for various conditions in vivo.
Various optical imaging techniques have been proposed. Such techniques may be applied in vivo to measure the thicknesses of tissue layers, study tissue structures, detect the presence of and/or spatial distribution of certain molecules or types of molecules in the tissues and the like.
In general, compared to non-optical methods, optical measurement techniques provide higher resolution and accuracy. Such techniques can approach the utility offered by histology images. However, conventional optical instrumentation cannot be readily used in endoscopic applications because the instrumentation is too large.
Various confocal imaging arrangements have been proposed for applications in vivo. In a confocal tissue imaging apparatus a spot of light is focused to a point in tissue. Backscattered light from the point in the tissue is collected and analyzed. The point at which the light is focused can be scanned through the tissue to provide a confocal image of the tissue. As with other optical imaging apparatus, it is a challenge to miniaturize confocal imaging apparatus to the point that it is small enough to use in certain applications. For example, it would be desirable to provide a miniature confocal imaging probe that is small enough to pass through the instrument channel of an endoscope that is typically a few millimeters in diameter. Another challenge is to avoid imaging artifacts arising from motions of the confocal imaging apparatus, Such motions arise mainly due to involuntary movements of the subject's body. Providing an imaging device capable of very rapid scanning of an area of tissue is one way to reduce the effect of such artifacts on image quality.
Two-dimensional tissue images may be provided in various planes. So-called ‘vertical section’ images are taken in planes extending into the tissue at least generally perpendicular to a surface of the tissue. Vertical section images are advantageous in part because pathology samples are typically prepared as vertical sections and pathologists and other medical professionals are trained to recognize features in vertical section images. Vertical section images also directly show the thickness of various tissue layers. Such layers are often arranged parallel to the tissue surface. Thickness measurements of biological tissues are useful for studying pathological processes and diseases. For instance, the thickening of epithelium in the vocal folds is an indicator of early laryngeal cancer. Another example is the measurement of the central corneal thickness that can be related to the intraocular pressure (TOP) to determine onset of glaucoma.
So-called horizontal sectional images are taken in planes extending generally parallel to the tissue surface. Three-dimensional images, are also useful for studying pathological processes and diseases.